Anticancer Identification and Molecular Docking of Cowanol from Garcinia fusca Against Histone Deacetylase Domains

Abstract

The inhibition of HDAC activity is presently one of the main targets for anticancer drug development. This study aimed to investigate the anticancer effect of cowanol via inhibition of HDAC and apoptosis induction in leukemic Jurkat cells. Computational analysis and HDAC inhibitor screening assays were used to determine the properties of cowanol as an HDAC inhibitor in Jurkat cells. MTT assays and Hoechst staining were performed to observe the cytotoxicity and apoptotic induction effect of cowanol. In silico docking analysis revealed that cowanol could tightly bind to the active sites of both HDAC class I (HDAC 2 and 8) and HDAC class II (HDAC 4 and 7) with a similar mode of binding to the reference inhibitors. Importantly, cowanol obviously interacts with the zinc ion at the catalytic center as well as with other amino acid residues in the active region, indicating its possible function as an HDAC inhibitor. The ADME results showed that cowanol possessed acceptable pharmacokinetics and drug-likeness properties, which suggested oral bioavailability. In addition, the screening assay demonstrated that cowanol could inhibit HDAC at 20-60 % compared to the standard HDAC inhibitor, SAHA. Moreover, the cytotoxic effect of cowanol against Jurkat cells with the IC50 was 18.19 ± 0.44 µM. For the mode of cell death, nuclear condensation and apoptotic bodies were characterized, supporting the role of the apoptosis inducer cowanol. Hence, our results indicated a potential new role of cowanol as an HDAC inhibitor. The cytotoxic mode of cowanol was illustrated as apoptotic inducer, which is a well-known target for anticancer drug development.